DESCRIPTION (applicant's abstract): Uncontrolled aggressive behavior is a serious social problem. Several rodent models of aggression have been developed to understand the neurobiological bases of aggression with the goal of developing pharmacological interventions. One common feature of these rodent models of aggression is that brain serotonin concentrations tend to be inversely correlated with aggressive behavior. A new model of intense, unrelenting aggression has been developed using mice that have the gene encoding the neuronal isoform of nitric oxide synthase (nNOS) selectively deleted. Male nNOS-/- mice display persistent aggression against other males, and persistent mounting attempts toward wild-type (WT) anestrous females. Female nNOS-/- mice do not display elevated agonistic behaviors in intruder-resident or neutral arena tests of aggression. The goal of the proposed studies is to examine the sex difference in aggressive behavior of nNOS-/- mice, and to determine the contribution of serotonin in aggressive behavior of nNOS-/- mice. There are four specific aims of the proposed studies: (1) to use a pharmacological manipulation, 7-nitroindazole (a specific nNOS antagonist), to confirm the observation that nNOS is important in mediating aggression, (2) to determine the contribution of sex steroid hormones to the sex difference in aggressive behavior among nNOS-/- mice, (3) to establish if female nNOS-/- mice display increased maternal aggression relative to WT mice, and (4) to determine the role of serotonin in the mediation of aggression in nNOS-/- animals.